The present invention relates generally to medicinal compositions and the use thereof; and more particularly, it relates to compositions of biologically active peptides and amino acid derivatives useful in the treatment of human neoplastic disease.
The practically infinite variety of peptides that can be formed by the combination of the twenty common amino acids has prompted many investigators to suggest that peptides may constitute a system carrying information from cell to cell and organ to organ. Following this view on the regulatory significance of peptides, researchers have isolated urinary peptides and amino acid derivatives which exert an influence on blood pressure, behavior modification, cardiovascular regulation, ahnd smooth muscle activity.
Accordingly, it has been considered by a number of researchers that neoplastic growth may be controlled by naturally occurring biochemical defense mechanisms. The immunological process has most often been attributed with antineoplastic activity. (See, for example, Aoki et al, Prog. Exp. Tumor Res., 19: 23 (1974)). There are, however, other possible mechanisms.
It has been suggested that neoplasia is a disease of cell differentiation. Given large number of differentiating cells and assuming the possibility of error in the program for differentiation, groups of abnormally growing cells can often arise under the influence of carcinogenic factors. Without a reliable mechanism for "normalizing" such erroneously developed cells, the organisms would not live very long. Such a mechanism should be able to correct the growth of newly developed neoplastic cells and direct them into normal differentiation pathways. It is Applicant's belief that peptides are ideal compounds to function as information-carrying molecules regulating cell differentiation.
In recent years, Applicant has described a number of medium-sized peptides and amino acid derivatives which demonstrated inhibition of DNA synthesis and mitosis in cultures of various neoplastic cells without significant inhibition of normal cell replication. (See Burzynski, Physiol. Chem. Phys., 5: 437 (1973); Burzynski et al, Fed. Proc., 32: 766 (1973); Burzynski et al, Physiol. Chem. Phys. 8: 13 (1976); Burzynski et al, Fed. Proc., 35: 623 (1976); Gross et al, Physiol. Chem. Phys., 8: 275 (1976); Burzynski et al, Physiol. Chem. Phys., 9: 485 (1977); Burzynski, U.S. Pat. Nos. 4,470,970 and 4,558,057.)